Illicitly Manufactured Fentanyl: Anesthesia’s Role in the Perioperative Setting

BackgroundGiven the opioid overdose crisis, surveillance of evolving opioid use patterns is critical to the effective deployment of mitigation strategies. The National Survey on Drug Use and Health (NSDUH) provided the first annual US estimate of illicitly manufactured fentanyl (IMF) use in 2022. However, as a household survey, NSDUH may not capture the full extent of population heroin and IMF use. We compare estimates of past-year heroin and IMF use and correlates of use in NSDUH and the Survey of Non-Medical Use of Prescription Drugs (NMURx) survey which employ an alternate sampling strategy.MethodsWe conducted a cross-sectional analysis of the 2022 NSDUH and NMURx. NSDUH samples respondents using a probability-based approach targeting community-dwelling individuals, while NMURx samples respondents using an opt-in, online survey panel. US adults ages 18 years and older were included. The main outcomes were differences in the weighted percentage of population reporting past-year use of heroin, IMF, and either heroin or IMF between the surveys. Secondary outcomes were the patterns of association of past-year heroin or IMF use with comorbid substance use, treatment utilization, and demographic characteristics between the surveys. Data were analyzed March to June 2024.ResultsNSDUH (n = 47,100 respondents) had a lower proportion of respondents who identified as non-Hispanic White and graduated college, and a higher proportion with past week employment than NMURx (N = 59,041 respondents). Past-year use of heroin, IMF, and either heroin or IMF were lower in the NSDUH than the NMURx. NSDUH estimated 0.52% (95% CI: 0.40%, 0.69%) %) of the US population used either heroin or IMF in the past year compared to 1.05% (95% CI: 0.97%, 1.14 0) in NMURx. In regression models, stimulant and benzodiazepine use were consistently associated with increased heroin or IMF use across both surveys.Conclusions and relevanceThe estimated prevalence of heroin or IMF use was nearly 50% higher in the NMURx compared to NSDUH. These results highlight the importance of using complementary surveillance approaches to obtain accurate estimates of the prevalence and patterns of heroin or IMF use.

Illicit opioids, particularly illicitly manufactured fentanyl (IMF), are major contributors to overdose deaths in the US. Understanding the prevalence and characteristics of illicit opioid use is crucial for addressing the opioid crisis. To estimate the prevalence of illicit opioid use, including IMF, and initial opioid exposure among those reporting illicit opioid use. This cross-sectional study was conducted using an online survey with targeted demographic quotas from June 10, 2024, to June 17, 2024. A total of 1515 participants aged 18 years and older from the US completed the survey. The analysis was conducted between June 30, 2024, and February 13, 2025. The primary outcome was self-reported illicit opioid use within the past 12 months. Secondary outcomes included initial exposure to opioids and perceived likelihood of overdose. Logistic regression was used to analyze associations with demographic and geographic factors. A total of 1515 respondents completed the survey, including 770 female individuals (50.8%), 20 American Indian or Alaska Native (1.3%), 101 Asian or Pacific Islander (6.7%), 215 Black (14.2%), 1087 White (81.7%), and 24 multiracial (1.6%); 186 (12.3%) were aged 18 to 24, 242 (16.0%) 25 to 34, 327 (21.6%) 35 to 44, 280 (18.5%) 45 to 54, 281 (18.5%) 55 to 64, 139 (9.2%) 65 to 74, and 60 (4.0%) 75 to 84 years. Among this sample, 166 (10.96%; 95% CI, 9.38%-12.52%) reported nonprescription opioid use within the past 12 months, including 114 (7.52%; 95% CI, 6.20%-8.85%) of the 1515 respondents reporting IMF use. Among those reporting nonprescription opioid use within the past 12 months, 65 (39.16%; 95% CI, 31.73%-46.58%) reported that their first opioid use involved opioids prescribed to them, whereas 60 (36.14%; 95% CI, 28.84%-43.45%) reported that their first use involved prescription opioids not prescribed to them. Only 41 (24.70%; 95% CI, 18.14%-31.26%) answered that their first exposure involved illicit opioids. Seventy-one (4.69%; 95% CI, 3.62%-5.75%) of all respondents reported that it was very likely they would have an overdose due to opioid use. This rate increased to 33.33% (95% CI, 24.68%-41.99%) among those who had used IMF within the past 12 months. Illicit opioid use was higher among men, Black respondents, and younger age groups. The findings of this cross-sectional study indicate a higher prevalence of illicit opioid use than previously reported, highlighting the need for more timely and accurate data to inform policy and intervention strategies. Enhanced data collection efforts are essential for understanding and mitigating the opioid crisis.

Opioid Drug Use and Acute Cardiac Events Among Pregnant Women in the United States

Illicitly Manufactured Fentanyl Use Among Individuals in the U.S., 2022

Trends in Opioid Use Among Adults With Cardiovascular Disease, 2001 - March 2020.

Background Chronic opioid use has turned into a global health challenge. Crohn’s disease (CD) patients may experience severe pain requiring opioids which could exacerbate CD symptoms and pose a risk of chronic use. The use of opioids among CD patients has not been explored on a national level. We compared the secular trends of opioid use among prevalent CD patients and matched reference individuals in Sweden. Methods This nationwide cohort study included adults with a prevalent CD diagnosis who lived in Sweden for at least 12 consecutive months at some point between 1 January 2008 and 31 December 2020. For each patient, up to 10 reference individuals from the general population were matched on birth year, sex, calendar year, and place of residence. We retrieved the data on dispensed opioid prescriptions (opioid use) from the National Prescribed Drug Register. We defined opioid use as ≥1 filled prescription per calendar year. We also estimated the annual prevalence of ≥1 dispensation of weak (codeine combinations, tramadol, and Dextropropoxifen) and/or strong opioids (Oxycodone, Morphine, Hydromorphone, Fentanyl, Buprenorphine, Tapentadol, and Petidin). Results We identified 43,155 adult CD patients and 418,218 reference individuals (Table 1). The prevalence of opioid use was stable from 2008-2016. However, between 2017 and 2020 it decreased from 19.7% (95% CI: 19.2, 20.2) to 16.9% (95% CI: 16.2, 17.7) and from 8.5% (95% CI: 8.4, 8.7) to 6.9% (95% CI: 6.7, 7.1) among CD patients and reference individuals, respectively (Figure 1a). However, between 2008 and 2020, the prescription of strong opioids more than doubled among both CD patients (increasing from 4.3% [95% CI: 4.1, 4.6] to 11.5% [95% CI: 11.1, 11.8]), and reference individuals (increasing from 1.3% [95% CI: 1.3, 1.4] to 5.4% [95% CI: 5.3, 5.5]) (Figure 1b). In 2020, the last year of the observation, compared with males, both female CD patients (20.3% [19.7, 20.8] vs 9.3% [9.2, 9.5]) and their matched reference individuals (15.3% [14.8, 15.9] vs 7.1% [6.9, 7.2]) had a higher prevalence of annual opioid use. The secular trends of overall opioid use and increasing use of strong opioids were similar for males and females (data not shown). Conclusion Annual opioid use among prevalent CD patients in Sweden, a country with publicly-funded healthcare and access to modern CD treatment, was two-fold higher than in the general population in the last 13 years. The annual opioid use remained stable from 2008-2016 and slightly decreased from 2017-2020 for CD patients and reference individuals. During the same period, the use of strong opioids more than doubled for CD patients and the general population.

Objective Illicitly manufactured fentanyl (IMF) has emerged as a catalyst of the recent drug epidemic in the United States. To devise more targeted and effective prevention and treatment strategies, it is crucial to understand the demographics of the population who consumes IMF and their health and associated substance use risks. Therefore, this study explores the sociodemographic characteristics, health diagnoses, and drug injection practices of individuals reporting IMF use. Methods Data were derived from the 2022 National Survey on Drug Use Health, based on a nationally representative sample of non-institutionalized individuals aged 12 and older in the United States. Focusing on 306 adults who reported ever using IMF, we examined their sociodemographic characteristics, health diagnoses, and substance-related behaviors in comparison to adults with a drug use disorder who did not report IMF use, using logistic regression analyses. Results The majority of U.S. adults reporting IMF use were aged 35–64, male, non-Hispanic White, with a high school education or lower, never married, and had an annual household income below $40,000. Compared to adults with a drug use disorder who did not report IMF use, they were more likely to report heart conditions (AOR = 2.67, 95% CI = 1.29–5.54) and Hepatitis B or C (AOR = 8.35, 95% CI = 4.05–17.02). Nearly half of this group had an opioid use disorder (OUD) in the past year, and 65.7% (95% CI = 56.7–74.8) reported a history of injecting drugs. Conclusions To effectively curb the current drug epidemic, incorporating effective treatment for OUD and harm reduction strategies is crucial.

Although opioids are a mainstay for perioperative pain management in hip fracture patients, no studies have described changes in opioid use over the last two decades. The aim of this study was to describe time trends in opioid use in a population-based cohort of patients undergoing a first-time hip fracture surgery during 1997-2018. Opioid-naïve hip fracture patients >55 years old were identified in Danish medical databases (n = 115,962). By 2-year calendar periods, we calculated prevalence rates (PR) of opioid use in the four quarters after surgery (Q1-Q4). Corresponding prevalence rate ratios (PRR) with 1997-1998 as a reference were estimated with 95% confidence intervals. Further, we calculated the median morphine milligram equivalents (MME) for each quarter. For Q1, the PR of opioid use increased from 29% in 1997-1998 to 78% in 2017-2018 corresponding to a PRR of 2.7 (2.6-2.8). For Q4, the PR was 15% in 1997-1998, peaked in 2003-2004 and then decreased, but stayed high at 13% in 2017-2018. The median MME did not increase when comparing 2017-2018 with 1997-1998, irrespective of the quarter. Tramadol was most frequently used in 1997-1998 shifting to oxycodone in 2017-2018. The PRs of opioid use in Q1 after surgery increased substantially from 1997 to 2018, but this did not translate into increased opioid use up to 1 year after hip fracture surgery or higher dosage. Our findings underline the importance of sustained focus on opioid tapering, dosage and use of opioids with the lowest potential for addiction and other adverse events. Overall, opioid use in Q1 after hip fracture surgery increased 2.7 times from 1997 to 2018, but the doses and opioid use up to 1 year after surgery remained stable. Compared to elderly, younger patients were more likely to use opioid in Q1, while the tendency was opposite in Q2-Q4. The most used opioid type changed from tramadol to oxycodone. Our findings underline the importance of personalized opioid tapering and doses, and use of opioids with the lowest potential for addiction and other adverse events.

Illicitly manufactured fentanyl (IMF) increases overdose mortality, but its role in infectious disease transmission is unknown. We examined whether IMF use predicts hepatitis C virus (HCV) and human immunodeficiency virus (HIV) incidence among a cohort of people who inject drugs (PWID) in San Diego, California and Tijuana, Mexico. PWID were recruited during 2020-2022, undergoing semi-annual interviewer-administered surveys and HIV and HCV serological rapid tests through 2024. Cox regression was conducted to examine predictors of seroconversion considering self-reported IMF use as a 6-month lagged, time-dependent covariate. Of 398 PWID at baseline, 67% resided in San Diego, 70% were male, median age was 43 years, 42% reported receptive needle sharing, and 25% reported using IMF. HCV incidence was 14.26 per 100 person-years (95% confidence interval [CI]: 11.49-17.02), and HIV incidence was 1.29 (95% CI: .49-2.10). IMF was associated with HCV seroconversion, with a univariable hazard ratio (HR) of 1.64 (95% CI: 1.09-2.40), and multivariable HR of 1.57 (95% CI: 1.03-2.40). The direction of the relationship with HIV was similar, albeit not significant (HR 2.39; 95% CI: .66-8.64). We document a novel association between IMF and HCV seroconversion among PWID in Tijuana-San Diego. Few HIV seroconversions (n = 10) precluded our ability to assess if a similar relationship held for HIV. IMF's short half-life may destabilize PWID-increasing the need for repeat dosing and sharing smoking materials and syringes. New preventive care approaches may reduce HCV transmission in the fentanyl era.

Background Opioid use patterns among Asian patients with inflammatory bowel disease (IBD), and the impact of advanced therapy (AT) on opioid use, are not well understood. This study aimed to investigate trends in chronic opioid use and assess the impact of AT initiation on opioid use among Korean patients with IBD. Methods Data were extracted from the Korean Health Insurance Review and Assessment Service database for adult patients with IBD from 2010 to 2022. Chronic opioid use was defined as ≥90 days or ≥3 opioid prescriptions within a calendar year. Chronic opioid users were matched with non-chronic opioid users at a 1:3 ratio based on sex, age, and type of IBD. Analyses included Poisson regression, the McNemar test, and generalized estimating equation (GEE). Results Between 2010 and 2020, Chronic opioid use was more prevalent in patients with Crohn’s disease (CD) compared to those with ulcerative colitis (UC). The number and proportion of chronic opioid users among Korean patients with CD and UC increased significantly (p-values <0.0001 for both trends). In 2010, only 123 patients with CD (1.57%) and 113 patients with UC (0.54%) were classified as chronic opioid users. However, by 2020, these numbers rose sharply to 1,286 patients with CD (5.44%) and 1,087 patients with UC (1.97%). In the McNemar test, the number of opioid users significantly decreased following AT initiation (p-value <0.0001 for both CD and UC): a large number of patients discontinued opioids after initiating AT (1,639 patients with CD and 1,600 patients with UC), while only a small number of patients began opioids after initiating AT (681 patients with CD and 642 patients with UC). GEE analysis further demonstrated that AT was significantly effective in reducing the number of opioid users among patients with CD (odds ratio [OR] = 0.479, 95% confidence interval [95% CI] = 0.440–0.521, p-value <0.0001) and UC (OR = 0.844, 95% CI = 0.775–0.919, p-value = 0.0001). Conclusion Although opioid use among Korean patients with IBD has been on the rise, AT is effective in reducing the number of opioid users among patients with both CD and UC.

Opioid Prescribing in United States Health Systems, 2015 to 2019

This narrative review summarizes literature on pharmaceutical fentanyl's absorption, distribution, metabolism, and excretion patterns to inform research on illicitly manufactured fentanyl (IMF). Fentanyl is highly lipophilic, lending itself to rapid absorption by highly perfused tissues (including the brain) before redistributing from these tissues to muscle and fat. Fentanyl is eliminated primarily by metabolism and urinary excretion of metabolites (norfentanyl and other minor metabolites). Fentanyl has a long terminal elimination, with a documented secondary peaking phenomenon that can manifest as "fentanyl rebound." Clinical implications in overdose (respiratory depression, muscle rigidity, and "wooden chest syndrome") and opioid use disorder treatment (subjective effects, withdrawal, and buprenorphine-precipitated withdrawal) are discussed. The authors highlight research gaps derived from differences in medicinal fentanyl studies and IMF use patterns, including that medicinal fentanyl studies are largely conducted with persons who were opioid-naive, anesthetized, or had severe chronic pain and that IMF use is characterized by supratherapeutic doses and frequent and sustained administration patterns, as well as adulteration with other substances and/or fentanyl analogs. This review reexamines information yielded from decades of medicinal fentanyl research and applies elements of the pharmacokinetic profile to persons with IMF exposure. In persons who use drugs, peripheral accumulation of fentanyl may be leading to prolonged exposure. More focused research on the pharmacology of fentanyl in persons using IMF is warranted.

Illicitly manufactured fentanyl (IMF) presence has increased reports of buprenorphine precipitated withdrawal and may impact medication for opioid use disorder (MOUD) experiences and preferences. Cross-sectional survey administered by a clinical research coordinator of adults treated by an addiction consult team or bridge clinic who had prior experience with MOUD. Among 100 respondents surveyed, 36% identified as female, 11% black, 9% Hispanic, 79% white, 29% had stable housing, 93% used fentanyl, and 65% injected commonly. 51% were currently treated with methadone, 41% were currently treated with sublingual buprenorphine, 12% were currently treated with extended-release buprenorphine, and 1% were currently treated with extended-release naltrexone. Most reported their current MOUD managed withdrawal and cravings well; 83.7% for methadone, 70.4% for sublingual buprenorphine, and 91.7% for extended-release buprenorphine. 75.8% of participants who tried buprenorphine reported ever experiencing precipitated withdrawal. Even so, 43.1% of those not being treated with buprenorphine were willing to start. Two-thirds reported cravings or withdrawal had worsened since IMF and 55% said IMF impacted MOUD decision making; however, 59% did not feel more worried about taking MOUD since IMF. Most (86%) had heard about low-dose buprenorphine initiation, 52.3% of those who had heard of it had tried it, and 57.8% reported positive experiences. 40% had heard of high-dose buprenorphine, 60% of those tried it, and 54.2% had positive experiences. The factors most likely to increase participants' willingness to start MOUD were immediate access (85%), rapid titration (87%), hearing positive things from friends (82%), and getting MOUD from their doctor (63%). Despite IMF impacting withdrawal, cravings, and MOUD decision making, most patients felt MOUD managed symptoms well. Experiences with alternative buprenorphine initiations were positive. Access to low-barrier treatment with immediate medication initiation, aggressive dose escalation, office-based treatment, and peer-based messaging around MOUD may increase treatment uptake.

Trends in opioid analgesic use for headaches in US emergency departments

INTRODUCTION: Pain is a common symptom in chronic pancreatitis (CP) and has a significant impact on quality of life. Although a variety of pain management strategies exist, opioids are the most frequently used analgesic given their high oral bioavailability and activity at multiple neuropathic and visceral pain receptors. Limited data exists on the trends of opioid dependence in CP. Our aim is to characterize trends in opioid use in CP over the last 15 years. METHODS: We performed a retrospective analysis in the IBM Explorys database (1999–2018), a pooled, de-identified clinical database of over 63 million unique patients from 26 health care networks and 300 hospitals across the United States. At the time of analysis there were 63,656,680 patients. Patient populations were identified using SNOMED and ICD codes. Cochrane-Armitage testing analyzed trends in chronic opioid use among CP patients between 2004–2018. Subgroup analysis for gender, age, race, and insurance status were assessed. RESULTS: 83,650 adult patients (>18 years old) had CP. 7,220 patients with CP were opioid dependent. The odds of being opioid dependent if diagnosed with chronic pancreatitis was 21.90 (P < 0.0001). Over the 15-year period, opioid dependence in chronic pancreatitis patients has significantly increased (2.25% to 4.35%; P < 0.0001). Most significant increase is noted among Medicaid (P = 0.0004) and Caucasian (P = 0.0001) patients. CONCLUSION: We present the first study to assess trends in opioid dependence among patients with CP over the last 15 years. Pain management is a critical component of treating CP. Multiple patient-dependent factors influence pain scores and opioid use in CP patients, including a history of alcohol use and psychological comorbidities. Side effects and opioid hyperalgesia significantly hinders their efficacy for long-term pain control.3 Pain exacerbation is the most common reason for hospitalization in CP, resulting in significant cost to the health care system.9 Opioid use and hypoalbuminemia are the biggest patient-specific risk factors for being hospitalized. Our results indicate that chronic opioid use in CP has increased in the last 15 years. Given the risks and side effects of opioids, along with recent legislation that more strictly regulates dispensation, finding alternative pain management techniques is essential in maintaining good quality of life for these patients.